Prediction of coronary artery calcium progression in individuals with low Framingham Risk Score: the Multi-Ethnic Study of Atherosclerosis.

Objectives: This study sought to determine whether novel markers not involving ionizing radiation could predict coronary artery calcium (CAC) progression in a low-risk population.

Background: Increase in CAC scores over time (CAC progression) improves prediction of coronary heart disease (CHD) events. Due to radiation exposure, CAC measurement represents an undesirable method for repeated risk assessment, particularly in individuals with low predicted risk (Framingham Risk Score [FRS] <10%).

Methods: From 6,814 participants in MESA (Multi-Ethnic Study of Atherosclerosis), 2,620 individuals were classified as low risk for CHD events (FRS <10%) and had follow-up CAC measurement. In addition to traditional risk factors (RFs), various combinations of novel marker models were selected on the basis of data-driven, clinical, or backward stepwise selection techniques.

Results: Mean follow-up was 2.5 years. CAC progression occurred in 574 participants (22% overall; 214 of 1,830 with baseline CAC = 0 and 360 of 790 with baseline CAC >0). Addition of various combinations of novel markers to the base model (c statistic = 0.711) revealed improvements in discrimination of approximately only 0.005 each (c statistics 0.7158, 0.7160, and 0.7164) for the best-fit models. All 3 best-fit novel marker models calibrated well but were similar to the base model in predicting individual risk probabilities for CAC progression. The highest prevalence of CAC progression occurred in the highest compared with the lowest probability quartile groups (39.2% to 40.3% vs. 6.4% to 7.1%).

Conclusions: In individuals at low predicted risk according to FRS, traditional risk factors predicted CAC progression in the short term with good discrimination and calibration. Prediction improved minimally when various novel markers were added to the model.